tbuckley/cabot-search huggingface dataset:
Interferons as the First Choice of Cytoreduction in Essential Thrombocythemia and Polycythemia Vera
Authors: Joan How, Gabriela Hobbs
Journal: Journal of the National Comprehensive Cancer Network (2022)

Interferons are cytokines with immunomodulatory properties that have been used in the treatment of myeloproliferative neoplasms (MPNs) for decades. However, their widespread use has been hampered by their adverse effect profile and difficulty with administration. Recently there has been a resurgence of interest in the use of interferons in MPNs given the development of pegylated formulations with improved tolerability. Currently, treatments for polycythemia vera (PV) and essential thrombocythemia (ET) are targeted toward decreasing the risk of thrombotic complications, because there are no approved therapies that are known to modify disease. However, recent data on interferons in MPNs have suggested the potential for disease-modifying activity, including the achievement of molecular remission and sustained clinical response. This development has led to the question of whether interferons should move forward as the preferred frontline cytoreductive agent for ET and PV, and challenges the criteria currently used to initiate therapy. We review randomized controlled trial data evaluating interferon’s efficacy and tolerability in patients with ET and PV. We then consider the data in the context of interferon’s known advantages and disadvantages to address whether interferons should be the first choice for cytoreductive treatment in patients with ET and PV.
Healthcare Cost Trajectories in the Last 2 Years of Life Among Patients With a Solid Metastatic Cancer: A Prospective Cohort Study
Authors: Ishwarya Balasubramanian, Eric Finkelstein, Rahul Malhotra, Semra Ozdemir, Chetna Malhotra, _ _
Journal: Journal of the National Comprehensive Cancer Network (2022)

Most studies describe the "average healthcare cost trend" among patients with cancer. We aimed to delineate heterogeneous trajectories of healthcare cost during the last 2 years of life of patients with a metastatic cancer and to assess the associated sociodemographic and clinical characteristics and healthcare use.We analyzed a sample of 353 deceased patients from a cohort of 600 with a solid metastatic cancer in Singapore, and we used group-based trajectory modeling to identify trajectories of total healthcare cost during the last 2 years of life.The average cost trend showed that mean monthly healthcare cost increased from SGD $3,997 during the last 2 years of life to SGD $7,516 during the last month of life (USD $1 = SGD $1.35). Group-based trajectory modeling identified 4 distinct trajectories: (1) low and steadily decreasing cost (13%); (2) steeply increasing cost in the last year of life (14%); (3) high and steadily increasing cost (57%); and (4) steeply increasing cost before the last year of life (16%). Compared with the low and steadily decreasing cost trajectory, patients with private health insurance (β [SE], 0.75 [0.37]; P=.04) and a greater preference for life extension (β [SE], -0.14 [0.07]; P=.06) were more likely to follow the high and steadily increasing cost trajectory. Patients in the low and steadily decreasing cost trajectory were most likely to have used palliative care (62%) and to die in a hospice (27%), whereas those in the steeply increasing cost before the last year of life trajectory were least likely to have used palliative care (14%) and most likely to die in a hospital (75%).The study quantifies healthcare cost and shows the variability in healthcare cost trajectories during the last 2 years of life. Policymakers, clinicians, patients, and families can use this information to better anticipate, budget, and manage healthcare costs.
Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial
Authors: Rongbo Lin, Jinfeng Zhu, Yushuang Luo, Xia Lv, Mingqian Lu, Haihui Chen, Huichao Zou, Zhichun Zhang, Shaowei Lin, Milu Wu, Xiaofeng Li, Min Zhou, Shen Zhao, Liyu Su, Jiang Liu, Cheng Huang
Journal: Journal of the National Comprehensive Cancer Network (2022)

Background: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. Methods: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. Results: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 ( P &lt;.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 ( P =.024) among the 3 arms. No severe adverse event occurred in any arm. Conclusions: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.
Myeloproliferative Neoplasms, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology
Authors: Aaron T. Gerds, Jason Gotlib, Haris Ali, Prithviraj Bose, Andrew Dunbar, Amro Elshoury, Tracy I. George, Krishna Gundabolu, Elizabeth Hexner, Gabriela S. Hobbs, Tania Jain, Catriona Jamieson, Paul R. Kaesberg, Andrew T. Kuykendall, Yazan Madanat, Brandon McMahon, Sanjay R. Mohan, Kalyan V. Nadiminti, Stephen Oh, Animesh Pardanani, Nikolai Podoltsev, Lindsay Rein, Rachel Salit, Brady L. Stein, Moshe Talpaz, Pankit Vachhani, Martha Wadleigh, Sarah Wall, Dawn C. Ward, Mary Anne Bergman, Cindy Hochstetler
Journal: Journal of the National Comprehensive Cancer Network (2022)

The classic Philadelphia chromosome–negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia. Assessment of symptoms at baseline and monitoring of symptom status during the course of treatment is recommended for all patients. This article focuses on the recommendations as outlined in the NCCN Guidelines for the diagnosis of MPN and the risk stratification, management, and supportive care relevant to MF.
Publisher Correction: Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel–Lindau syndrome
Authors: Shuijie Li, Wenyu Li, Juan Yuan, Petra Bullova, Jieyu Wu, Xuepei Zhang, Yong Liu, Monika Plescher, Javier Rodriguez, Oscar C. Bedoya-Reina, Paulo R. Jannig, Paula Valente-Silva, Meng Yu, Marie Arsenian Henriksson, Roman A. Zubarev, Anna Smed-Sörensen, Carolyn K. Suzuki, Jorge L. Ruas, Johan Holmberg, Catharina Larsson, C. Christofer Juhlin, Alex von Kriegsheim, Yihai Cao, Susanne Schlisio
Journal: Nature Metabolism (2022)
Financial Toxicity and Its Association With Prostate and Colon Cancer Screening
Authors: Michael J. Herriges, Rachel Shenhav-Goldberg, Juliet I. Peck, Sumeet K. Bhanvadia, Alicia Morgans, Fumiko Chino, Thenappan Chandrasekar, Oleg Shapiro, Joseph M. Jacob, Alina Basnet, Gennady Bratslavsky, Hanan Goldberg
Journal: Journal of the National Comprehensive Cancer Network (2022)

The term "financial toxicity" or "hardship" is a patient-reported outcome that results from the material costs of cancer care, the psychological impacts of these costs, and the coping strategies that patients use to deal with the strain that includes delaying or forgoing care. However, little is known about the impact of financial toxicity on cancer screening. We examined the effects of financial toxicity on the use of screening tests for prostate and colon cancer. We hypothesized that greater financial hardship would show an association with decreased prevalence of cancer screening.This cross-sectional survey-based US study included men and women aged ≥50 years from the National Health Interview Survey database from January through December 2018. A financial hardship score (FHS) between 0 and 10 was formulated by summarizing the responses from 10 financial toxicity dichotomic questions (yes or no), with a higher score associated with greater financial hardship. Primary outcomes were self-reported occurrence of prostate-specific antigen (PSA) blood testing and colonoscopy for prostate and colon cancer screening, respectively.Overall, 13,439 individual responses were collected. A total of 9,277 (69.03%) people had undergone colonoscopies, and 3,455 (70.94%) men had a PSA test. White, married, working men were more likely to undergo PSA testing and colonoscopy. Individuals who had not had a PSA test or colonoscopy had higher mean FHSs than those who underwent these tests (0.70 and 0.79 vs 0.47 and 0.61, respectively; P≤.001 for both). Multivariable logistic regression models demonstrated that a higher FHS was associated with a decreased odds ratio for having a PSA test (0.916; 95% CI, 0.867-0.967; P=.002) and colonoscopy (0.969; 95% CI, 0.941-0.998; P=.039).Greater financial hardship is suggested to be associated with a decreased probability of having prostate and colon cancer screening. Healthcare professionals should be aware that financial toxicity can impact not only cancer treatment but also cancer screening.
FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma
Authors: Amro M. Abdelrahman, Ajit H. Goenka, Roberto Alva-Ruiz, Jennifer A. Yonkus, Jennifer L. Leiting, Rondell P. Graham, Kenneth W. Merrell, Cornelius A. Thiels, Christopher L. Hallemeier, Susanne G. Warner, Michael G. Haddock, Travis E. Grotz, Nguyen H. Tran, Rory L. Smoot, Wen Wee Ma, Sean P. Cleary, Robert R. McWilliams, David M. Nagorney, Thorvardur R. Halfdanarson, Michael L. Kendrick, Mark J. Truty
Journal: Journal of the National Comprehensive Cancer Network (2022)

Background: Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. Methods: We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). Results: We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P &lt;.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13–0.40), and was highly correlated ( P =.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor ( P &lt;.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9–153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2–0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1–0.4). Conclusions: Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.
Fecal Immunochemical Testing in Patients With Low-Risk Symptoms of Colorectal Cancer: A Diagnostic Accuracy Study
Authors: Alex J. Ball, Imran Aziz, Sophie Parker, Ravishankar B. Sargur, Jonathan Aldis, Matthew Kurien
Journal: Journal of the National Comprehensive Cancer Network (2022)

The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population.Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 μg hemoglobin per gram of feces (μg/g).A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 μg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 μg/g, respectively. The sensitivity of FIT at ≥10 μg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis.Utilization of FIT at a threshold ≥10 μg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.
Response to Selpercatinib in a Patient With Recurrent Glioblastoma and RET Amplification
Authors: Cameron Czech, Ashley Chen, Katherine P. Morgan, Carlos Zamora, Sherif El-Refai, Norleena Poynter, Simon Khagi
Journal: Journal of the National Comprehensive Cancer Network (2022)

Glioblastoma (GBM) is a malignant central nervous system neoplasm that remains largely incurable. Limited treatment options currently exist after disease progression on standard-of-care first-line therapy. However, repurposing the use of approved therapies in patients with potentially targetable genomic alterations continues to be an emerging area of interest. This report presents the first description of a patient with isocitrate dehydrogenase wild-type GBM with an underlying RET amplification who demonstrated a near-complete response while receiving therapy with the RET inhibitor selpercatinib. The case highlights the excellent blood-brain barrier penetration of selpercatinib, as well as its potential role in the management of RET -amplified GBM. Larger biomarker-enriched studies are needed to confirm the results of this case report. Given the rare incidence of RET alterations in GBM, findings from this report can help guide and support optimal treatment strategies for patients with RET -altered GBM.
Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations
Authors: Isabella Hetherington, Hana Totary-Jain
Journal: Molecular Therapy (2022)

Atherosclerosis is the main underlying pathology for many cardiovascular diseases (CVDs), which are the leading cause of death globally and represent a serious health crisis. Atherosclerosis is a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease. Elevated plasma lipids, hypertension, and high glucose are the major risk factors for developing atherosclerotic plaques. To date, most pharmacological therapies aim to control these risk factors, but they do not target the plaque-causing cells themselves. In patients with acute coronary syndromes, surgical revascularization with percutaneous coronary intervention has greatly reduced mortality rates. However, stent thrombosis and neo-atherosclerosis have emerged as major safety concerns of drug eluting stents due to delayed re-endothelialization. This review summarizes the major milestones, strengths, and limitations of current anti-atherosclerotic therapies. It provides an overview of the recent discoveries and emerging game-changing technologies in the fields of nanomedicine, mRNA therapeutics, and gene editing that have the potential to revolutionize CVD clinical practice by steering it toward precision medicine.
Diminished Expression of C/EBPα in Skin Carcinomas Is Linked to Oncogenic Ras and Reexpression of C/EBPα in Carcinoma Cells Inhibits Proliferation
Authors: Minsub Shim, Kristina L. Powers, Sarah J. Ewing, Songyun Zhu, Robert C. Smart
Journal: Cancer Research (2005)

Abstract The basic leucine zipper transcription factor, CCAAT/enhancer binding protein α (C/EBPα) is involved in mitotic growth arrest and has been implicated as a human tumor suppressor in acute myeloid leukemia. We have previously shown that C/EBPα is abundantly expressed in mouse epidermal keratinocytes. In the current study, the expression of C/EBPα was evaluated in seven mouse skin squamous cell carcinoma (SCC) cell lines that contain oncogenic Ha-Ras. C/EBPα mRNA and protein levels were greatly diminished in all seven SCC cell lines compared with normal primary keratinocytes, whereas C/EBPβ levels were not dramatically changed. Reexpression of C/EBPα in these SCC cell lines resulted in the inhibition in SCC cell proliferation. To determine whether the decrease in C/EBPα expression observed in the SCC cell lines also occurred in the carcinoma itself, immunohistochemical staining for C/EBPα in mouse skin SCCs was conducted. All 14 SCCs evaluated displayed negligible C/EBPα protein expression and normal C/EBPβ levels compared with the epidermis and all 14 carcinomas contained mutant Ras. To determine whether oncogenic Ras is involved in the down-regulation of C/EBPα, BALB/MK2 keratinocytes were infected with a retrovirus containing Ras12V, and C/EBPα protein, mRNA and DNA binding levels were determined. Keratinocytes infected with the retrovirus containing oncogenic Ras12V displayed greatly diminished C/EBPα protein, mRNA and DNA binding levels. In addition, BALB/MK2 cells containing endogenous mutant Ras displayed diminished C/EBPα expression and the ectopic expression of a dominant-negative RasN17 partially restored C/EBPα levels in these cells. These results indicate that oncogenic Ras negatively regulates C/EBPα expression and the loss of C/EBPα expression may contribute to the development of skin SCCs.
Citation indicators revisited: Reply to Top Authors in Dermatology
Authors: Mindy D. Szeto, Mayra B.C. Maymone, Colby L. Presley, Melissa R. Laughter, Steven M. Lada, Taylor M. Runion, Cara Barber, Allene S. Fonseca, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2022)
Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients
Authors: Yu Jun Wong, Chen Zhaojin, Guilia Tosetti, Elisabetta Degasperi, Sanchit Sharma, Samagra Agarwal, Liu Chuan, Chan Yiong Huak, Li Jia, Qi Xiaolong, Anoop Saraya, Massimo Primignani
Journal: Clinical and Molecular Hepatology (2022)

The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients.